TNFR2 Agonism: Basic Science and Promising Treatment for Multiple Sclerosis and Related Diseases

Area of Science:

• Neuroimmunology
• Neurobiology
• Demyelinating Diseases

Background:

• Multiple sclerosis (MS) is characterized by inflammation, demyelination, and neurodegeneration, with current therapies lacking comprehensive action.
• Axonal loss in MS leads to irreversible disability, highlighting the need for neuroprotective strategies.
• Existing MS treatments do not address all three core pathologies or offer neuroprotection.

Purpose of the Study:

• To explore tumor necrosis factor receptor 2 (TNFR2) as a therapeutic target for MS.
• To review the potential of TNFR2 agonism in countering MS pathologies and promoting neuroprotection.
• To discuss the development of TNFR2 agonist antibodies and their applications.

Main Methods:

• Review of basic science studies on TNFR2 agonism in MS models.
• Analysis of T-regulatory cell (Treg) induction by TNFR2 activation.
• Examination of recent advancements in TNFR2 agonist antibody design.

Main Results:

• TNFR2 agonism demonstrates immunosuppressive, neuroprotective, and pro-differentiation effects in MS models.
• TNFR2 activation potently induces T-regulatory cells (Tregs), particularly TNFR2-expressing Tregs, which offer significant suppression.
• TNFR2's restricted expression pattern suggests a favorable safety profile with minimized systemic side effects.

Conclusions:

• TNFR2 agonism presents a unique therapeutic strategy to address the multifaceted pathologies of MS.
• Targeting TNFR2 offers a potential pathway for neuroprotection and mitigating chronic disability in MS.
• Advancements in TNFR2 agonist antibody design may overcome previous therapeutic hurdles, opening new treatment avenues.